{"entity": "researcher", "timestamp": "2026-08-09T07:31:18.255Z", "family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "affiliations": ["Department of Molecular Medicine and Surgery Karolinska Institutet and Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111"}}, "publications": [{"entity": "publication", "iuid": "0b48959ee84c4ee890a0e427e268d9c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0b48959ee84c4ee890a0e427e268d9c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0b48959ee84c4ee890a0e427e268d9c6"}}, "title": "Novel activating SNRNP70-ALK fusion in congenital infant-type hemispheric glioma displays clinical response to lorlatinib: a case-report", "authors": [{"family": "Arthur", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-0645-6530", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b07104d934d413a9c9546e7e9933051.json"}}, {"family": "Georgantzi", "given": "Kleopatra", "initials": "K"}, {"family": "de St\u00e5hl", "given": "Teresita D\u00edaz", "initials": "TD"}, {"family": "Guan", "given": "Jikui", "initials": "J", "orcid": "0000-0003-1723-0307", "researcher": {"href": "https://publications.scilifelab.se/researcher/a39044157aa7475485fb489a003b63d1.json"}}, {"family": "Oder", "given": "Blaz", "initials": "B", "orcid": "0000-0001-7984-3104", "researcher": {"href": "https://publications.scilifelab.se/researcher/9851f9fc65fc44aea55d0c1567be7887.json"}}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Illies", "given": "Christopher", "initials": "C"}, {"family": "Sandgren", "given": "Johanna", "initials": "J", "orcid": "0000-0001-6776-2649", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d5b6b16fdbe470f83de8748227f8987.json"}}, {"family": "Svoboda", "given": "Jan", "initials": "J"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Barbany", "given": "Gisela", "initials": "G", "orcid": "0000-0003-3185-2962", "researcher": {"href": "https://publications.scilifelab.se/researcher/13fda0d702d543f981898ebd53849817.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Sandvik", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-9273-2158", "researcher": {"href": "https://publications.scilifelab.se/researcher/72b8c0bf76054dc8ba15fa80fa78918e.json"}}, {"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a683cea1874ac290d91c325a648be8.json"}}, {"family": "Hallberg", "given": "Bengt", "initials": "B"}, {"family": "Palmer", "given": "Ruth", "initials": "R", "orcid": "0000-0002-2735-8470", "researcher": {"href": "https://publications.scilifelab.se/researcher/808281ecc2634b66a274895e58a122bd.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal-article", "published": "2026-02-26", "journal": {"title": "NPJ Precis Oncol", "issn": "2397-768X", "volume": "10", "issue": "1", "issn-l": null}, "abstract": "We report a child with an antenatally detected brain tumor that progressed over three years' time despite surgery, chemo- and proton therapy. Retrospective whole-genome and transcriptome sequencing with methylation analysis of primary tumor tissue led to the molecular diagnosis infant-type hemispheric glioma, and identified a novel SNRNP70::ALK fusion, providing a therapeutic target for compassionate-use precision treatment with the ALK tyrosine kinase inhibitor lorlatinib. Functional studies confirmed the fusion protein to be expressed and active in the patient's tumor. After two years of therapy, the child has sustained partial tumor regression on MRI and no new neurological symptoms. We conclude that comprehensive multi-omics analyses are required for correct molecular diagnosis in childhood CNS tumors and can radically impact patient outcome by identifying molecular targets for precision treatment.", "doi": "10.1038/s41698-026-01336-x", "pmid": "41748687", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12996540"}, {"db": "pii", "key": "10.1038/s41698-026-01336-x"}], "notes": [], "created": "2026-03-23T15:20:36.846Z", "modified": "2026-03-24T09:13:14.286Z"}, {"entity": "publication", "iuid": "0ab446dce183413fb52d603c3a2acc32", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ab446dce183413fb52d603c3a2acc32.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ab446dce183413fb52d603c3a2acc32"}}, "title": "The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma.", "authors": [{"family": "Krynina", "given": "Olha", "initials": "O", "orcid": "0009-0006-6911-557X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b89f0ad136bf4c11aa69fdf2137f6db1.json"}}, {"family": "de St\u00e5hl", "given": "Teresita D\u00edaz", "initials": "TD"}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Arthur", "given": "Cecilia", "initials": "C"}, {"family": "Giraud", "given": "Geraldine", "initials": "G"}, {"family": "Nyman", "given": "Per", "initials": "P"}, {"family": "Fritzberg", "given": "Anders", "initials": "A"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}, {"family": "Sandvik", "given": "Ulrika", "initials": "U"}], "type": "journal article", "published": "2024-01-24", "journal": {"title": "Neurooncol Adv", "issn": "2632-2498", "volume": "6", "issue": "1", "pages": "vdae008", "issn-l": null}, "abstract": "Low-grade gliomas (LGGs) represent children's most prevalent central nervous system tumor, necessitating molecular profiling to diagnose and determine the most suitable treatment. Developing highly sensitive screening techniques for liquid biopsy samples is particularly beneficial, as it enables the early detection and molecular characterization of tumors with minimally invasive samples.\n\nWe examined CSF and plasma samples from patients with pilocytic astrocytoma (PA) using custom multiplexed droplet digital polymerase chain reaction (ddPCR) assays based on whole genome sequencing data. These assays included a screening test to analyze BRAF duplication and a targeted assay for the detection of patient-specific KIAA1549::BRAF fusion junction sequences or single nucleotide variants.\n\nOur findings revealed that 5 out of 13 individual cerebrospinal fluid (CSF) samples tested positive for circulating tumor DNA (ctDNA). Among these cases, 3 exhibited the KIAA1549::BRAF fusion, which was detected through copy number variation (CNV) analysis (n = 1) or a fusion-specific probe (n = 2), while 1 case each displayed the BRAF V600E mutation and the FGFR1 N577K mutation. Additionally, a quantitative analysis of cell-free DNA (cfDNA) concentrations in PA CSF samples showed that most cases had low cfDNA levels, below the limit of detection of our assay (<1.9 ng).\n\nWhile CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations, for example, to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.", "doi": "10.1093/noajnl/vdae008", "pmid": "38371226", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10874216"}, {"db": "pii", "key": "vdae008"}], "notes": [], "created": "2024-11-25T10:25:46.645Z", "modified": "2025-02-28T14:19:16.581Z"}, {"entity": "publication", "iuid": "14f4d2b869aa4a2dabad06efa432aa96", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14f4d2b869aa4a2dabad06efa432aa96.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14f4d2b869aa4a2dabad06efa432aa96"}}, "title": "Simultaneous Ultra-Sensitive Detection of Structural and Single Nucleotide Variants Using Multiplex Droplet Digital PCR in Liquid Biopsies from Children with Medulloblastoma.", "authors": [{"family": "Arthur", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-0645-6530", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b07104d934d413a9c9546e7e9933051.json"}}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "de St\u00e5hl", "given": "Teresita D\u00edaz", "initials": "TD", "orcid": "0000-0001-5933-6623", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f51158ce6e14f3b96bf16a214689d1d.json"}}, {"family": "Shamikh", "given": "Alia", "initials": "A"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Harila", "given": "Arja", "initials": "A"}, {"family": "Barbany", "given": "Gisela", "initials": "G", "orcid": "0000-0003-3185-2962", "researcher": {"href": "https://publications.scilifelab.se/researcher/13fda0d702d543f981898ebd53849817.json"}}, {"family": "Sandvik", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-9273-2158", "researcher": {"href": "https://publications.scilifelab.se/researcher/72b8c0bf76054dc8ba15fa80fa78918e.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2023-03-25", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "15", "issue": "7", "issn-l": "2072-6694"}, "abstract": "Medulloblastoma is a malignant embryonal tumor of the central nervous system (CNS) that mainly affects infants and children. Prognosis is highly variable, and molecular biomarkers for measurable residual disease (MRD) detection are lacking. Analysis of cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) using broad genomic approaches, such as low-coverage whole-genome sequencing, has shown promising prognostic value. However, more sensitive methods are needed for MRD analysis. Here, we show the technical feasibility of capturing medulloblastoma-associated structural variants and point mutations simultaneously in cfDNA using multiplexed droplet digital PCR (ddPCR). Assay sensitivity was assessed with a dilution series of tumor in normal genomic DNA, and the limit of detection was below 100 pg of input DNA for all assays. False positive rates were zero for structural variant assays. Liquid biopsies (CSF and plasma, n = 47) were analyzed from 12 children with medulloblastoma, all with negative CSF cytology. MRD was detected in 75% (9/12) of patients overall. In CSF samples taken before or within 21 days of surgery, MRD was detected in 88% (7/8) of patients with localized disease and in one patient with the metastasized disease. Our results suggest that this approach could expand the utility of ddPCR and complement broader analyses of cfDNA for MRD detection.", "doi": "10.3390/cancers15071972", "pmid": "37046633", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10092983"}, {"db": "pii", "key": "cancers15071972"}], "notes": [], "created": "2023-11-29T11:43:56.624Z", "modified": "2024-01-16T13:48:33.819Z"}, {"entity": "publication", "iuid": "8f4af9fc1bd845f8bc456a6a13cd3e34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f4af9fc1bd845f8bc456a6a13cd3e34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f4af9fc1bd845f8bc456a6a13cd3e34"}}, "title": "Sensitive Detection of Cell-Free Tumour DNA Using Optimised Targeted Sequencing Can Predict Prognosis in Gastro-Oesophageal Cancer.", "authors": [{"family": "Wallander", "given": "Karin", "initials": "K", "orcid": "0000-0001-8166-9678", "researcher": {"href": "https://publications.scilifelab.se/researcher/db174787efd74dc1b84f1bf56b74a22d.json"}}, {"family": "Haider", "given": "Zahra", "initials": "Z", "orcid": "0000-0002-0759-3932", "researcher": {"href": "https://publications.scilifelab.se/researcher/4084e066170543e699dd116c8e7c05df.json"}}, {"family": "Jeggari", "given": "Ashwini", "initials": "A", "orcid": "0000-0002-7155-9050", "researcher": {"href": "https://publications.scilifelab.se/researcher/083131be9eab46df9c789fb018316dff.json"}}, {"family": "Foroughi-Asl", "given": "Hassan", "initials": "H"}, {"family": "Gellerbring", "given": "Anna", "initials": "A"}, {"family": "Lyander", "given": "Anna", "initials": "A"}, {"family": "Chozhan", "given": "Athithyan", "initials": "A"}, {"family": "Cuba Gyllensten", "given": "Ollanta", "initials": "O"}, {"family": "H\u00e4gglund", "given": "Moa", "initials": "M", "orcid": "0000-0003-3765-4342", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3de7b5aa952454e81d0ff55056c33a0.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Lindblad", "given": "Mats", "initials": "M"}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2023-02-11", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "15", "issue": "4", "pages": null}, "abstract": "In this longitudinal study, cell-free tumour DNA (a liquid biopsy) from plasma was explored as a prognostic biomarker for gastro-oesophageal cancer. Both tumour-informed and tumour-agnostic approaches for plasma variant filtering were evaluated in 47 participants. This was possible through sequencing of DNA from tissue biopsies from all participants and cell-free DNA from plasma sampled before and after surgery (n = 42), as well as DNA from white blood cells (n = 21) using a custom gene panel with and without unique molecular identifiers (UMIs). A subset of the plasma samples (n = 12) was also assayed with targeted droplet digital PCR (ddPCR). In 17/31 (55%) diagnostic plasma samples, tissue-verified cancer-associated variants could be detected by the gene panel. In the tumour-agnostic approach, 26 participants (59%) had cancer-associated variants, and UMIs were necessary to filter the true variants from the technical artefacts. Additionally, clonal haematopoietic variants could be excluded using the matched white blood cells or follow-up plasma samples. ddPCR detected its targets in 10/12 (83%) and provided an ultra-sensitive method for follow-up. Detectable cancer-associated variants in plasma correlated to a shorter overall survival and shorter time to progression, with a significant correlation for the tumour-informed approaches. In summary, liquid biopsy gene panel sequencing using a tumour-agnostic approach can be applied to all patients regardless of the presence of a tissue biopsy, although this requires UMIs and the exclusion of clonal haematopoietic variants. However, if sequencing data from tumour biopsies are available, a tumour-informed approach improves the value of cell-free tumour DNA as a negative prognostic biomarker in gastro-oesophageal cancer patients.", "doi": "10.3390/cancers15041160", "pmid": "36831507", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9954085"}, {"db": "pii", "key": "cancers15041160"}], "notes": [], "created": "2023-11-22T21:52:05.588Z", "modified": "2023-11-22T21:52:13.584Z"}, {"entity": "publication", "iuid": "fe32db42a23d4b0493233edb03d30535", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fe32db42a23d4b0493233edb03d30535.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fe32db42a23d4b0493233edb03d30535"}}, "title": "TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy", "authors": [{"family": "Whitman", "given": "Mary C", "initials": "MC", "orcid": "0000-0001-6297-7499", "researcher": {"href": "https://publications.scilifelab.se/researcher/21394272a53249128f071b3534003852.json"}}, {"family": "Barry", "given": "Brenda J", "initials": "BJ", "orcid": "0000-0003-4358-8126", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb5fd7a40d2f403c9bf2b997253e8b82.json"}}, {"family": "Robson", "given": "Caroline D", "initials": "CD", "orcid": "0000-0001-5592-249X", "researcher": {"href": "https://publications.scilifelab.se/researcher/628b1225b1ca4051bda76538e5e34e5e.json"}}, {"family": "Facio", "given": "Flavia M", "initials": "FM", "orcid": "0000-0002-7472-471X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f9f2ce92355417da97ed9718f71b687.json"}}, {"family": "Van Ryzin", "given": "Carol", "initials": "C"}, {"family": "Chan", "given": "Wai Man", "initials": "WM", "orcid": "0000-0002-2888-4739", "researcher": {"href": "https://publications.scilifelab.se/researcher/31a0389fd412422baed8522a3f99bbc9.json"}}, {"family": "Lehky", "given": "Tanya J", "initials": "TJ", "orcid": "0000-0001-6421-505X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee74d5adf8f549f09fe60b8200875bff.json"}}, {"family": "Thurm", "given": "Audrey", "initials": "A", "orcid": "0000-0002-0489-9485", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c2492121444452da5bd557759d92331.json"}}, {"family": "Zalewski", "given": "Christopher", "initials": "C", "orcid": "0000-0002-9196-0589", "researcher": {"href": "https://publications.scilifelab.se/researcher/3461307cef854119acdaddc2dc7a1fba.json"}}, {"family": "King", "given": "Kelly A", "initials": "KA"}, {"family": "Brewer", "given": "Carmen", "initials": "C"}, {"family": "Almpani", "given": "Konstantinia", "initials": "K"}, {"family": "Lee", "given": "Janice S", "initials": "JS"}, {"family": "Delaney", "given": "Angela", "initials": "A", "orcid": "0000-0002-0632-6365", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1dd90cef7494fb6ac110ea34fff7a4f.json"}}, {"family": "FitzGibbon", "given": "Edmond J", "initials": "EJ", "orcid": "0000-0001-6855-7540", "researcher": {"href": "https://publications.scilifelab.se/researcher/047ac05ae35841edbc71ea4691f12ff8.json"}}, {"family": "Lee", "given": "Paul R", "initials": "PR"}, {"family": "Toro", "given": "Camilo", "initials": "C", "orcid": "0000-0002-3917-9031", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea4b48adf194d1da8bee3e5cc6f73f4.json"}}, {"family": "Paul", "given": "Scott M", "initials": "SM", "orcid": "0000-0003-1274-6670", "researcher": {"href": "https://publications.scilifelab.se/researcher/f393b70fb6084204862be0aa29633d8b.json"}}, {"family": "Abdul-Rahman", "given": "Omar A", "initials": "OA"}, {"family": "Webb", "given": "Bryn D", "initials": "BD"}, {"family": "Jabs", "given": "Ethylin Wang", "initials": "EW", "orcid": "0000-0001-8983-5466", "researcher": {"href": "https://publications.scilifelab.se/researcher/557e871f5783485d9921259c01a04c52.json"}}, {"family": "Moller", "given": "Hans Ulrik", "initials": "HU"}, {"family": "Larsen", "given": "Dorte Ancher", "initials": "DA"}, {"family": "Antony", "given": "Jayne H", "initials": "JH"}, {"family": "Troedson", "given": "Christopher", "initials": "C"}, {"family": "Ma", "given": "Alan", "initials": "A", "orcid": "0000-0002-9293-4753", "researcher": {"href": "https://publications.scilifelab.se/researcher/67c70ee5b7bd4136a74d7605ec7b1614.json"}}, {"family": "Ragnhild", "given": "Glad", "initials": "G", "orcid": "0000-0002-8067-4616", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7e76c6d53d14bca835a983181115271.json"}}, {"family": "Wirgenes", "given": "Katrine V", "initials": "KV", "orcid": "0000-0002-0649-7850", "researcher": {"href": "https://publications.scilifelab.se/researcher/9de12d69eb8c49c190bc6e11c593766f.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Maarup", "given": "Timothy James", "initials": "TJ", "orcid": "0000-0001-9268-6246", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3a0adaa44a44669b31c0d37285f393.json"}}, {"family": "MacKinnon", "given": "Sarah", "initials": "S"}, {"family": "Hunter", "given": "David G", "initials": "DG", "orcid": "0000-0002-4587-4794", "researcher": {"href": "https://publications.scilifelab.se/researcher/64847b06ddf54437b375a15dae3d2347.json"}}, {"family": "Collins", "given": "Francis S", "initials": "FS", "orcid": "0000-0002-1023-7410", "researcher": {"href": "https://publications.scilifelab.se/researcher/10628a7a84cb4c7dbd6c161a8723ccbb.json"}}, {"family": "Manoli", "given": "Irini", "initials": "I", "orcid": "0000-0003-1543-2941", "researcher": {"href": "https://publications.scilifelab.se/researcher/01d08f2e55bf4b299f2f084b5b39cf48.json"}}, {"family": "Engle", "given": "Elizabeth C", "initials": "EC", "orcid": "0000-0001-8194-7738", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e771e3512f64184bd65fa90221c0eb1.json"}}], "type": "journal-article", "published": "2021-12-00", "journal": {"title": "Hum Genet", "issn": "0340-6717", "issn-l": "0340-6717", "volume": "140", "issue": "12", "pages": "1709-1731"}, "abstract": "Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.", "doi": "10.1007/s00439-021-02379-9", "pmid": "34652576", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1757235"}, {"db": "pmc", "key": "PMC8656246"}, {"db": "pii", "key": "10.1007/s00439-021-02379-9"}], "notes": [], "created": "2021-11-20T12:24:26.995Z", "modified": "2023-06-19T11:00:25.410Z"}, {"entity": "publication", "iuid": "87bf78d535ce41dbbf344f9db435066f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/87bf78d535ce41dbbf344f9db435066f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/87bf78d535ce41dbbf344f9db435066f"}}, "title": "Massive parallel sequencing in individuals with multiple primary tumours reveals the benefit of re-analysis.", "authors": [{"family": "Wallander", "given": "Karin", "initials": "K"}, {"family": "Thonberg", "given": "H\u00e5kan", "initials": "H", "orcid": "0000-0003-4503-4717", "researcher": {"href": "https://publications.scilifelab.se/researcher/481958db26a2433ea8d5cc786c3b2bca.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2021-10-28", "journal": {"title": "Hered Cancer Clin Pract", "issn": "1731-2302", "volume": "19", "issue": "1", "pages": "46", "issn-l": null}, "abstract": "Multiple primary cancers, defined as three or more primary tumours, are rare, and there are few genetic studies concerning them. There is a need for increased knowledge on the heritability of multiple primary cancers and genotype-phenotype correlations. We have performed whole-genome/exome sequencing (WGS/WES) in ten individuals with three or more primary tumours, with no previous findings on standard clinical genetic investigations. In one individual with a clinical diagnosis of MEN1, a likely pathogenic cryptic splice site variant was detected in the MEN1 gene. The variant (c.654C > A) is synonymous but we showed in a cDNA analysis that it affects splicing and leads to a frameshift, with the theoretical new amino acid sequence p.(Gly219Glufs*13). In one individual with metachronous colorectal cancers, ovarian cancer, endometrial cancer and chronic lymphocytic leukaemia, we found a likely pathogenic variant in the MLH1 gene (c.27G > A), and two risk factor variants in the genes CHEK2 and HOXB13. The MLH1 variant is synonymous but has previously been shown to be associated to constitutional low-grade hypermethylation of the MLH1 promoter, and segregates with disease in families with colorectal and endometrial cancer. No pathogenic single nucleotide or structural variants were detected in the remaining eight individuals in the study. The pathogenic variants found by WGS/WES were in genes already sequenced by Sanger sequencing and WES in the clinic, without any findings. We conclude that, in individuals with an unequivocal clinical diagnosis of a specific hereditary cancer syndrome, where standard clinical testing failed to detect a causative variant, re-analysis may lead to a diagnosis.", "doi": "10.1186/s13053-021-00203-z", "pmid": "34711244", "labels": {"Clinical Genomics Stockholm": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13053-021-00203-z"}, {"db": "pmc", "key": "PMC8555269"}], "notes": [], "created": "2021-11-20T12:31:14.384Z", "modified": "2024-01-16T13:48:38.170Z"}, {"entity": "publication", "iuid": "d91cc3feeee74452a935028588037c31", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d91cc3feeee74452a935028588037c31.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d91cc3feeee74452a935028588037c31"}}, "title": "Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients.", "authors": [{"family": "Wallander", "given": "Karin", "initials": "K"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Lindblad", "given": "Mats", "initials": "M"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Billiau", "given": "Kenny", "initials": "K"}, {"family": "Foroughi", "given": "Hassan", "initials": "H", "orcid": "0000-0002-6925-9040", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7aaee1f82c9436da604fb9046db0dae.json"}}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Lied\u00e9n", "given": "Agne", "initials": "A"}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2021-02-04", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "16", "issue": "2", "pages": "e0245488", "issn-l": "1932-6203"}, "abstract": "Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer.\n\nDNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other.\n\nCancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients.\n\nWe conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer.", "doi": "10.1371/journal.pone.0245488", "pmid": "33539436", "labels": {"Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-14603"}, {"db": "pmc", "key": "PMC7861431"}], "notes": [], "created": "2021-11-20T12:24:01.447Z", "modified": "2024-01-16T13:48:40.771Z"}, {"entity": "publication", "iuid": "d7d67ba83c054a63b3e9e39989da1cf5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7d67ba83c054a63b3e9e39989da1cf5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7d67ba83c054a63b3e9e39989da1cf5"}}, "title": "Exome sequencing in 51 early onset non-familial CRC cases.", "authors": [{"family": "Thutkawkorapin", "given": "Jessada", "initials": "J", "orcid": "0000-0001-9306-844X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa13464dfebd4c868fe4eb1f0186a41b.json"}}, {"family": "Lindblom", "given": "Annika", "initials": "A"}, {"family": "Tham", "given": "Emma", "initials": "E", "orcid": "0000-0001-6079-164X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6689dd9aff584082a57398141a538111.json"}}], "type": "journal article", "published": "2019-05-00", "journal": {"volume": "7", "issn": "2324-9269", "issue": "5", "pages": "e605", "title": "Mol Genet Genomic Med", "issn-l": "2324-9269"}, "abstract": "Colorectal cancer (CRC) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi-allelic autosomal recessive pathogenic variants.\n\nThe cohort was whole exome sequenced (WES) at 100\u00d7 coverage. Both a dominant- and recessive model were used for searching predisposing genetic factors. In addition, we assayed recessive variants of potential moderate risk that were enriched in our young-onset CRC cohort. Variants were filtered using a candidate cancer gene list or by selecting variants more likely to be pathogenic based on variant type (e.g., loss-of-function) or allele frequency.\n\nWe identified one pathogenic variant in PTEN in a patient subsequently confirmed to have a hereditary hamartoma tumor syndrome (Cowden syndrome) and one patient with a pathogenic heterozygous variant in PMS2 that was originally not identified by WES due to low quality reads resulting from pseudogenes. In addition, we identified three heterozygous candidate missense variants in known cancer susceptibility genes (BMPR1A, BRIP1, and SRC), three truncating variants in possibly novel cancer genes (CLSPN, SEC24B, SSH2) and four candidate missense variants in ACACA, NR2C2, INPP4A, and DIDO1. We also identify five possible autosomal recessive candidate genes: ATP10B, PKHD1, UGGT2, MYH13, TFF3.\n\nTwo clear pathogenic variants were identified in patients that had not been identified clinically. Thus, the chance of detecting a hereditary cancer syndrome in patients with CRC at young age but without family history is 2/51 (4%) and therefore the clinical benefit of genetic testing in this patient group is low. Of note, using stringent filtering, we have identified a total of ten candidate heterozygous variants and five possibly biallelic autosomal recessive candidate genes that warrant further study.", "doi": "10.1002/mgg3.605", "pmid": "30809968", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6503031"}], "notes": [], "created": "2019-04-23T10:00:11.219Z", "modified": "2024-01-16T13:48:44.415Z"}]}